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بخشی از مقاله انگلیسیعنوان انگلیسی:Implications of laboratory diagnosis on brucellosis therapy~~en~~

Brucellosis is a worldwide zoonosis with a huge economic impact on animal husbandry and public health. The diagnosis of human brucellosis can be protracted because the disease primarily presents as fever of unknown origin with unspecific clinical signs and symptoms. The isolation rate of the fastidious etiologic agent from blood cultures is low, and therefore laboratory diagnosis is mainly based on serologic and molecular testing. However, seronegative brucellosis patients have been described, and antibody titers of diagnostic significance are difficult to define. Whether the molecular detection of Brucella DNA in clinical samples should be followed by long-term antibiotic treatment or not is also a matter of debate. The aim of this article is to review and discuss the implications of laboratory test results in the diagnosis of human brucellosis on disease therapy.

Brucellosis is one of the world’s most widespread bacterial zoonoses, leading to tremendous economic losses in endemic regions and serious complaints in affected patients. The infection may be transmitted by direct animal contact, but is usually acquired through the consumption of contaminated food products of animal origin, mainly via unpasteurized goat’s milk and cheese. Furthermore, brucellosis is the most common bacterial laboratory-acquired infection worldwide [1]. Although many national and international programs have been established to eradicate the pathogen and control its spreading in animal husbandry, brucellosis is still a re-emerging disease. The surveillance of animal brucellosis is difficult due to bacterial persistence in wildlife and environmental reservoirs, with consecutive spill-over to domestic animals [2].

Brucellosis is caused by members of the genus Brucella (B.), which are gram-negative, facultative intracellular coccobacilli that were historically differentiated by their preferred animal host, varying pathogenicity and a few selected phenotypic traits. The genus comprises six classical species: B. melitensis bv 1–۳ (primarily isolated from sheep and goats); B. abortus bv 1–۶ and 9 (from cattle and other Bovidae); B. suis bv 1–۳ (from pigs), bv 4 (from reindeer), bv 5 (from small rodents); B. canis (from dogs); B. ovis (from sheep); and B. neotomae (from desert wood rats). Recently, two novel species of marine origin, B. pinnipedialis (isolated from seals) and B. ceti (from dolphins and whales) [3], B. microti isolated from the common vole (Microtus arvalis) [4], red foxes (Vulpes vulpes) [5] and from soil [6], and B. inopinata isolated from a breast implant wound of a 71-year-old female patient [7] have been described. In the past, a lot of atypical Brucella strains arose. These could represent novel species or lineages of already described species, for example various Brucella strains originating from wild native rodent species in North Queensland, Australia [8], a novel Brucella isolate in association with two cases of stillbirth in nonhuman primates [9], and a B. inopinata-like strain (BO2), which was isolated from a lung biopsy of a 52-year-old Australian patient suffering from chronic destructive pneumonia [10].

Physicians’ awareness of the infection is very poor in many countries, and most cases correctly identified are clinically advanced. Because of its protean clinical manifestations, human brucellosis can be easily confused with other infectious and noninfectious diseases, leading to diagnostic delays and late onset of therapy. The isolation of the fastidious organisms is often unsuccessful or takes a long time, which is why the presumptive clinical diagnosis is usually confirmed by serologic tests. However, seronegative cases, cross-reactivity of anti-Brucella antibodies with many other clinically relevant bacteria, poorly defined cutoffs in serologic test systems, and so on can make the interpretation of the titers measured very difficult. Alternatively, molecular techniques can be used for the laboratory diagnosis of human brucellosis, but the detection of Brucella DNA does not prove an active infection with viable bacteria, and therefore does not effectively support therapeutic decision making.

The scope of this article is to review up-to-date laboratory techniques in the diagnosis of human brucellosis and to discuss if positive serologic or molecular tests should result in long-term antibiotic therapy.

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